miR-24 Exerts Its Anticancer Effect by Inhibiting Protective Autophagy of Pancreatic Cancer Mediated by Silica Nanoparticles

Abstract

Autophagy plays a key role in protecting cells against injury caused by foreign substances and maintaining the stability of cells. Nanomaterials easily cause cell autophagy, as foreign substances. In this experiment, we explored whether overexpressing miR-24 protects autophagy response of pancreatic cancer mediated by silica nanoparticles. Silica nanoparticles were first characterized and then used to treat pancreatic cancer cells in a co-culture system. Pancreatic cancer cells were divided into blank group (no transfection), miR-24 group (miR-24 mimics transfection), and control group (miR-24 inhibitors transfection). Immunohistochemistry (IHC) and immunoblots were used to monitor the expression of autophagy gene Beclin-1 and LC3-II. Transmission electron microscopy (TEM) was used to observe the formation of autophagosomes. The diameters of silica nanoparticles were about 100 nm before and after modification, with uniform size, high dispersion, and a negative potential state. The silica nanoparticles caused fluorescence aggregation in many pancreatic cancer cells, significantly increasing the LC3-I and LC3-II, and promoted the cytoprotective autophagy ability of pancreatic cancer cells. Transfection of miR-24 significantly inhibited Beclin-1 and LC3-II. Western blots also confirmed that the miR-24 significantly suppressed Beclin-1 and LC3-II. TEM results suggested that the miR-24 transfection significantly inhibited the release of autophagosomes. Silica nanomaterials can cause the protective autophagy response of pancreatic cancer cells and increase LC3-I and LC3-II. miR-24 can significantly inhibit the protective autophagy of pancreatic cancer cells caused by silica nanoparticles and suppressed Beclin-1 and LC3-II. miR-24 can also inhibited the release of autophagosomes in pancreatic cancer cells to inhibit the protective autophagy.